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Thursday, November 1, 2012

72 is the New 30?!!

Everyone knows that human life expectancies have been improving. But just how extraordinary and incomparable that improvement has been is not widely understood. Demographers Oskar Burgera, Annette Baudischa, and James W. Vaupel offer two remarkable sets of comparisons in "Human mortality improvement in evolutionary context," which appears in a recent issue of the Proceedings of the Natural Academy of Sciences (October 30, 2012, vol. 109, no. 44, 18210-18214). From their abstract:

"The health and economic implications of mortality reduction have been given substantial attention, but the observed malleability of human mortality has not been placed in a broad evolutionary context. We quantify the rate and amount of mortality reduction by comparing a variety of human populations to the evolved human mortality profile, here estimated as the average mortality pattern for ethnographically observed hunter-gatherers. We show that human mortality has decreased so substantially that the difference between hunter-gatherers and today’s lowest mortality populations is greater than the difference between hunter-gatherers and wild chimpanzees. The bulk of this mortality reduction has occurred since 1900 and has been experienced by only about 4 of the roughly 8,000 human generations that have ever lived. Moreover, mortality improvement in humans is on par with or greater than the reductions in mortality in other species achieved by laboratory selection experiments and endocrine pathway mutations."

Their first main set of comparisons is to look at human mortality declines in a very long-run evolutionary context: from hunter-gatherers to modern humans. They focus to some extent on modern Sweden and Japan as examples of the highest life expectancies for modern humans (in what follows "y" is the writers' abbreviation for "years, and footnotes and references to figures are omitted).

"That is, Swedes in 1900 had mortality profiles closer to hunter-gatherers than to the Swedes of today. This relative difference between Swedes recently and those 100 y ago has emerged in a rapid revolutionary leap, as this distance is far greater than that between hunter-gatherers and chimps. The recent jumps in mortality reduction are remarkable in the context of mammal diversity because age-specific death rates for hunter-gatherers are already exceptionally low, probably among the lowest of any nonhuman primate or terrestrial mammal (especially if body size is controlled for), and lower than even captive chimpanzees at all ages. The human mortality profile, however, is so plastic that over the past century the populations doing best managed to achieve very large reductions in death rates that were already low compared with those of other species. ...

"For example, hunter-gatherers at age 30 have the same probability of death as present-day Japanese at the age of 72: hence the age of a person in Japan that is equivalent to a 30-y-old hunter-gatherer is 72. In other words, compared with the evolutionary pattern, 72 is the new 30. ...

"In gross comparative terms, this means that during evolution from a chimp-like ancestor to anatomically modern humans, mortality levels once typical of prime-of-life individuals were pushed back to later ages at the rate of a decade every 1.3millions years, but the mortality levels typical of a 15-y-old in 1900 became typical of individuals a decade older about every 30 y since 1900."

Their second main set of comparisons is to look at the gain in human mortality compared with the gains in mortality achieved in laboratory situations, by manipulating the genetics and the environment of fruit flies, nematode worms, mice, and the like.

"Fruit fly selection experiments achieve significant extensions in life span by rearing successive generations from eggs laid by old individuals. In one classic example, mean life span increased by about 30% in 15 generations , for a rate of change of almost 2% per generation, and in another by about 100% in 13 generations, or just over 5% per generation. For human hunter-gatherers, mean life span at birth is about 31 ... For Swedes, it was about 32 in 1800, 52 in 1900, and is 82 today. So life expectancy increased by about 165% from hunter-gatherers to modern Swedes and at a rate of about 12% per generation since 1800.

"Some of the most promising directions for understanding the physiological mechanisms of aging come from experiments with mutations that affect the endocrine pathway. These impressive experiments have extended mean life span in nematode worms by >100%, fruit flies by ∼85% , and laboratory mice by ∼50%. Dietary restriction, which involves suppressing caloric intake of an organism, has extended life span in nematodes by 100–200%, fruit flies by ∼100%, and mice by ∼50%. Hence recent human mortality improvement is often greater than that achieved by manipulated strains of model organisms relative to the wild type, especially when single mutations orphysiological pathways are manipulated. However, experiments that simultaneously manipulate multiple pathways in organisms such as yeast and nematode worms can achieve much greater life span extensions. The majority of laboratory studies where mammals are the model organism have been done on mice and yield percentage life span increases less than those gained by humans."

It's unclear just what the recent changes in human life expectancy mean for the long run, because they are so without parallel either in the evolutionary record or in the lab. It seems unlikely that the huge gains in human life expectancy since 1900 or so can be related to large changes in genetics or physiological processes: not enough generations have passed. As the authors ask: "Why does the human genome give humans a license to drastically reduce mortality by nongenetic change?" The answer is not yet clear, but what is clear is that there is a "biologically unique" plasticity in the human mortality decline that has already occurred.